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NCT Number: NCT07406230

Methotrexate Early Toxicity Monitoring

High-dose methotrexate (MTX) is the main componement of first line treatment in primary central nervous system lymphoma. Renal toxicity is the main dose limiting toxicity because of major MTX elimination by the kidneys. MTX crystallizes in renal tubules, leading to a renal failure (RF) and further delaying its elimination. When RF occurs, MTX accumulates, prolonging the duration of treatment exposure. MTX prolonging exposure can cause life-threatening complications and delay further treatments in the patient. Preventive measures have been developped, such as alkaline fluid hyperhydration and folic acid administration, to try to reduce the risk of these adverse events.

In suspected severe RF in link to MTX is suspected, glucarpidase can be administared. However, this is an expensive treatment and not all patients recover normal renal function despite its use.

MTX is an essential treatment for the management of PCNSL which is currently a curable disease especially in patients who are able to receive a consolidation treatment as thiotepa-based intensive consolidation followed by autologous stem cell transplantation (IC-ASCT). IC-ASCT requires a normal renal function, which could be impaired by severe RF secondary to MTX.

The purpose of the study is to investigate how early dosing MTX could be used to simulate late concentrations. Early monitoring of MTX elimination could be implemented to identify patients at risk of delayed elimination and thus introduce rapid mesures as early administration of glucarpidase.

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Key information

Conditions

Primary Central Nervous System Lymphoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

Location contact

Laurence SCHENONE

CONTACT

Laurence SCHENONE

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patient aged 18 years or older,
  • Patient with a primary lymphoma of the central nervous system, histologically or cytologically proven,
  • Patient eligible for high-dose methotrexate treatment (> at 500 mg/m 2), in the first line of treatment,
  • Patient who has received information regarding the study and signed an informed consent,
  • Patient beneficiary or entitled to a social security scheme.

Exclusion criteria

  • Patient treated with a therapy complementary to the standard 1st-line treatment based on high-dose MTX as part of a clinical research protocol,
  • Patient in a period of exclusion from another research protocol at the time of signing consent,
  • Subjects covered by articles L1121-5 to 1121-8 of the Public Health Code (minor patient, adult patient under guardianship or curatorship, patient deprived of liberty, pregnant or breastfeeding woman).

Treatment and study plan

methotrexate plasmatic dosing

Other

Methotrexate (MTX) dosage at 2,4,6,8,24 and 48 hours

Primary outcomes

  1. Accuracy measurement of Bayesian model

    Time frame: 48 hours post MTX

    Determine, in patients with Primary Central Nervous System Lymphoma (PCNL), the most efficient Bayesian model for predicting the delay in MTX elimination using a pharmacometry approach (in silico modeling based on a population approach) based on the early dosage of methotrexate in plasma.

Secondary outcomes

  1. Determine the Bayesian model for predicting renal toxicity of MTX T48H using a pharmacometric approach (in silico modeling) based on early dosing of methotrexate in plasma

    Time frame: 48 hours post MTX

    Renal toxicity shall be defined as acute renal failure graded according to CTCAE V5 in relation to the value of serum creatinine before administration of MTX.

  2. Determine the bayesian model for predicting MTX clearance 72 hours after MTX using a pharmacometric approach (in silico modeling) based on early dosing of methotrexate in plasma

    Time frame: 72 hours post MTX

    Delay in elimination will be defined by a methotrexate dosage 72 hours after administration (T72H) beyond 0.2 μmol/L.

  3. Estimate in an exploratory approach the performance of the Bayesian model for predicting the delay in MTX elimination at 48 hours using a pharmacometric approach (in silico modeling)

    Time frame: 48 hours post

    Correlation between, early dosage of methotrexate in plasma and other parameters of interest measured at baseline (before MTX administration) such as patient age, albumin and creatinine clearance.

  4. Estimate in an exploratory approach the performance of the Bayesian model for predicting overexposure to MTX at 48 hours using a pharmacometric approach (in silico modeling)

    Time frame: 48 hours post MTX

    Correlation between, early dosage of methotrexate in plasma and other parameters of interest measured at baseline (before MTX administration) such as patient age, albumin and creatinine clearance. Overexposure to MTX is defined by a measured T48H > 10 μmol/L.

Study contacts

Contact information is provided by the study sponsor or research team.

Laurence SCHENONE

CONTACT

[email protected]

04 91 38 55 00 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique Hopitaux De Marseille

Other

Registry information

Official study title

Methotrexate Early Toxicity Monitoring in Primary Central Nervous System Lymphomas (PCNSL)

Acronym: METoxiM

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Feb 12, 2026
Registry last updated
Feb 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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